Environmental pollutants are important contributors to human disease, particularly cancer. The long-term goal of the studies proposed here is to increase our understanding of the interactions between foreign compounds and cellular macromolecules; we are particularly interested in those interactions which lead to phenotypic changes, such as increases in microsomal drug-metabolizing enzyme activity or neoplastic transformation. One series of experiments will evaluate the potential usefulness of reactive small molecules in the study of chromatin structure. The approach will be to chemically modify chromatin, using the reactive forms of various chemical carcinogens. We will ask whether differences in the level of chromain organization or alterations in chromatin conformation affect the relative ability of the various chromatin components to undergo modification. Such experiments will complement other studies which employ macromolecular probes (enzymes) to study chromatin structure. A study series of experiments will evaluate the usefulness of reactive metabolic intermediates as affinity labels, for identifying specific acceptor molecules within the cell. We will focus initially on the use of benzo(a)pyrene diol-epoxide I (BPDE) as an affinity label, because polycyclic aromatic hydrocarbons (PAHs) are potent inducers of the microsomal mixed-function oxygenase, aryl hydrocarbon hydroxylase, and a cytoplasmic receptor protein has been implicated in the induction mechanism. We will ask whether BPDE can be used to identify 1) specific cytoplasmic and/or nuclear proteins with properties characteristic of those of receptors and 2) microsomal and/or nuclear membrane proteins which preferentially interact with PAHs. Such experiments may lead to a better understanding of the molecular mechanisms involved in microsomal enzyme induction, the toxicity of foreign compounds, and chemical carcinogenesis.